Purified and delipidated cytochrome oxidase isolated from beef heart mitochondria into detergent particles and reconstituted into single-walled lipid bilayer vesicles are being characterized by freeze-etch electron microscopy; light scattering; differential scanning calorimetry; optical, laser-resonance-Raman, esr and nmr spectroscopy; and X-ray absorption and scattering measurements. Particular attention is given to: (1) defining the environment of the Fe and Cu sites and their charge states; (2) mapping of the geometrical distribution of these metal atoms in the protein; and (3) ascertaining the influence of lipid environment on the conformation of the protein and on its activity as assayed by the rate of the mediated electron transfer between ferrocytochrome-c and molecular oxygen. The question of lipid-mediated protein-protein interaction is also being addressed.